癌症研究
先天免疫系统
免疫疗法
干扰素基因刺激剂
肿瘤微环境
CpG站点
免疫
免疫系统
癌症免疫疗法
材料科学
DNA甲基化
免疫学
生物
基因
生物化学
基因表达
作者
Xiaojing Chen,Qianyun Tang,Jinqiang Wang,Yan Zhou,Fengqin Li,Yuexia Xie,Xingang Wang,Ling Du,Junru Li,Jun Pu,Quanyin Hu,Zhen Gu,Peifeng Liu
标识
DOI:10.1002/adma.202210440
摘要
Immunotherapy has achieved revolutionary success in clinics, but it remains challenging for treating hepatocellular carcinoma (HCC) characterized by high vascularization. Here, it is reported that metal-organic framework-801 (MOF-801) can be employed as a stimulator of interferon genes (STING) through Toll-like receptor 4 (TLR4) not just as a drug delivery carrier. Notably, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) and 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) STING agonist with vascular disrupting function coordinates with MOF-801 to self-assemble into a nanoparticle (MOF-CpG-DMXAA) that effectively delivers CpG ODNs and DMXAA to cells for synergistically improving the tumor microenvironment by reprogramming tumor-associated macrophages (TAMs), promoting dendritic cells (DCs) maturation, as well as destroying tumor blood vessels. In HCC-bearing mouse models, it is demonstrated that MOF-CpG-DMXAA triggers systemic immune activation and stimulates robust tumoricidal immunity, resulting in a superior immunotherapeutic efficiency in orthotopic and recurrent HCC.
科研通智能强力驱动
Strongly Powered by AbleSci AI